Petah Tikva, Israel
Petah Tikva, Israel

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Fulcher G.,University of Sydney | Singer J.,Endocrine Institute | Castaneda R.,Hospital General Regional No 1 Dr Carlos Mac Gregor Sanchez Navarro | Fraige Filho F.,University of Sao Paulo | And 3 more authors.
Journal of Medical Economics | Year: 2014

Objectives: To understand the impact of nocturnal and daytime non-severe hypoglycemic events on healthcare systems, work productivity and quality of life in people with type 1 or type 2 diabetes.Methods: People with diabetes who experienced a non-severe hypoglycemic event in the 4 weeks prior to the survey were eligible to participate in a nocturnal and/or daytime hypoglycemia survey. Surveys were conducted in Argentina, Australia, Brazil, Israel, Mexico and South Africa.Results: In total, 300 respondents were included in nocturnal/daytime hypoglycemia surveys (50/participating country/survey). All respondents with type 1 diabetes and 68%/62% (nocturnal/daytime) with type 2 diabetes were on insulin treatment. After an event, 25%/30% (nocturnal/daytime) of respondents decreased their insulin dose and 39%/36% (nocturnal/daytime) contacted a healthcare professional. In the week after an event, respondents performed an average of 5.6/6.4 (nocturnal/daytime) additional blood glucose tests. Almost half of the respondents (44%) reported that the event had a high impact on the quality of their sleep. Among nocturnal survey respondents working for pay, 29% went to work late, 16% left work early and 12% reported missing one or more full work days due to the surveyed event. In addition, 50%/39% (nocturnal/daytime) indicated that the event had a high impact on their fear of future hypoglycemia.Conclusions: The findings suggest that nocturnal and daytime non-severe hypoglycemic events have a large financial and psychosocial impact. Diabetes management that minimizes hypoglycemia while maintaining good glycemic control may positively impact upon the psychological wellbeing of people with diabetes, as well as reducing healthcare costs and increasing work productivity. © 2014 Informa UK Ltd.


Melamud L.,Multiple Sclerosis Center | Golan D.,Multiple Sclerosis Center | Luboshitzky R.,Endocrine Institute | Luboshitzky R.,Technion - Israel Institute of Technology | And 3 more authors.
Journal of the Neurological Sciences | Year: 2012

Background: Sleep disruption and fatigue are common in Multiple Sclerosis (MS). Melatonin is one of the major regulators of sleep-wake cycle. The role of melatonin in MS-related sleep disturbances and fatigue as well as the interaction between melatonin and Interferon beta (IFN-β) treatment were the subject of this study. Objective: To assess the influence of IFN-β treatment on melatonin secretion, fatigue and sleep characteristics in patients with MS. Methods: 13 MS patients and 12 healthy controls participated. Fatigue was evaluated using the Fatigue Impact Scale (FIS), sleep was assessed by actigraphy and day/night levels of 6-sulphatoxy-melatonin (6-SMT) in urine were determined using a highly specific ELISA assay. Results: Naïve MS patients demonstrated significantly decreased levels of 6-SMT and disrupted circadian regulation of its secretion, which were increased with IFN-β treatment, in association with improved fatigue. Sleep Efficiency was significantly lower in the MS group compared to controls. Conclusion: Our findings suggest dysregulation of Melatonin secretion in MS, which may be influenced by IFN-β treatment. The results call for further characterization of the role of neuro-hormones such as melatonin in MS, and their cross-regulation with immune-mediators. © 2011 Elsevier B.V. All rights reserved.


Luboshitzky R.,Endocrine Institute | Ishay A.,Endocrine Institute | Herer P.,Endocrine Institute
Endocrinologist | Year: 2010

It is not clear whether or not subclinical hypothyroidism (SH) is associated with an increased risk for cardiovascular disease.We prospectively examined 43 women with SH and 49 healthy controls of similar age.Fasting blood levels of thyrotropin, free thyroxin, antibodies to thyroid peroxidase and thyroglobulin, glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and insulin were measured. Body mass index, waist and hip circumferences, blood pressure, homeostasis model assessment 2-insulin resistance index, and the presence of metabolic syndrome (MS) were also evaluated.Mean systolic blood pressure was increased in SH patients versus controls (128.6 vs. 120.7 mm Hg; P = 0.04). Mean values of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and insulin were not different in patients with SH compared with controls. SH had significantly higher triglyceride levels (1.50 ± 0.65 mmol/L) and glucose levels (5.26 ± 0.63 mmol/L) compared with controls (1.27 ± 0.59, 5.05 ± 0.52; P = 0.04, P = 0.04, respectively). Although body mass index values were similar in both groups, patients had greater waist circumference than controls (90.7 ± 13 cm vs. 81.8 ± 10.6; P = 0.0007). The percentages of patients with SH having hypertension (34.1%), hypertriglyceridemia (37.2%), hyperglycemia (20.9%), and greater waist circumference (51.2%) were higher than the percentages in controls. Thus, the percentage of MS in patients (41.5%) was significantly higher than in controls (12.2%; P = 0.003). SH had significantly higher likelihood of cardiovascular risks (odds ratio, 6.26; 95% confidence interval, 1.6-4.49; P = 0.008 for MS).We conclude that SH is associated with greater probability of MS. This may increase the risk of accelerated atherosclerosis and premature cardiovascular disease in these patients. © 2010 by Lippincott Williams & Wilkins.


Dvorkin S.,Endocrine Institute | Robenshtok E.,Endocrine Institute | Robenshtok E.,Tel Aviv University | Hirsch D.,Endocrine Institute | And 6 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Background: Evaluation of surgical specimens suggests that patients with Hashimoto thyroiditis (HT) have a higher prevalence of differentiated thyroid cancer. Although patients with HT are reported to present with earlier stage disease, there is controversy as to whether these patients have better prognosis when adjusted for histology and stage at presentation. Objectives: To investigate differences between patients with differentiated thyroid cancer patients and without HT for aggressiveness of disease and clinical outcome, and the decline rate of antithyroglobulin antibodies titers over time. Methods: A retrospective study using the Rabin Medical Center Thyroid Cancer Registry. Seven hundred fifty-three patients were included and divided into 2 groups of patients with and without HT at diagnosis. Disease severity at presentation was evaluated using the entire cohort, whereas a control group matched for age, gender, histology, and stage was used to evaluate disease course and outcome. Results: HT was present in 14.2% (n = 107) of included patients and was associated with smaller primary tumor (17.9 vs 21.2 mm, P = .01) and less lymph node involvement (23% vs 34%, P = .02) at presentation. When matched groups were compared, patients with HT received less additional radioactive iodine (RAI) treatments (1.24 vs 1.45, P = .03) and showed lower rates of persistence at 1 year (13% vs 26%, P = .04) and higher rates of disease remission at the end of follow-up (90% vs 79%, P = .05). On multivariate analysis HT was predictive of a lower rate of lymph nodes involvement (odds ratio 0.34, 95% confidence interval 0.17-0.66) and persistent disease at the end of follow-up (odds ratio 0.48, 95% confidence interval 0.24-0.93). Antithyroglobulin antibodies slowly disappeared in most patients with no evidence of disease. Conclusion: Our study demonstrates that HT is associated with a less aggressive form of differentiated thyroid cancer and a better long-term outcome. Copyright © 2013 by The Endocrine Society.


Ishay A.,Endocrine Institute | Ishay A.,Technion - Israel Institute of Technology | Herer P.,Endocrine Institute | Luboshitzky R.,Endocrine Institute | Luboshitzky R.,Technion - Israel Institute of Technology
Endocrine Practice | Year: 2011

Objective: To evaluate the effect of parathyroidectomy on metabolic abnormalities associated with cardiovascular disease in patients with primary hyperparathyroidism (PHPT).Methods: Thirty-four patients with PHPT (aged 51.0 ± 11.8 years, mean ± standard deviation) underwent assessment before and 1 year after successful parathyroidectomy. A control group of 42 normocalcemic healthy subjects, matched for age and body mass index, was also examined at baseline. We measured serum lipids, glucose, insulin, uric acid, calcium, parathyroid hormone, C-reactive protein, and bone density. Insulin resistance index was evaluated by homeostasis model assessment, and the presence of metabolic syndrome was determined. Because of multiple tests, the level of statistical significance was set at.01.Results: After parathyroidectomy, there was a decrease in diastolic blood pressure (P<.02) and in serum concentrations of uric acid (P<.04) and insulin (P<.009). No difference was observed in rates of metabolic syndrome in patients before and 1 year after parathyroidectomy (23.5% versus 17.6%; P>.46). Insulin resistance index values were also unchanged from before to after parathyroidectomy (1.3 ± 0.9 and 1.1 ± 0.9, respectively; P>.68). A substantial increase in spine bone density (5%; P<.05) was noted postoperatively. Multivariate logistic regression analysis, after adjustment for age and body mass index, revealed that parathyroidectomy did not lead to a significant decrease in likelihood of cardiovascular risk-odds ratio (OR), 1.82; 95% confidence interval (CI), 0.53 to 6.21 (P>.34) for the metabolic syndrome and OR, 0.82; 95% CI, 0.17 to 3.88 (P>.8) for the insulin resistance index.Conclusion: In this study, surgical treatment had no beneficial effect on cardiovascular risk, as assessed by the metabolic syndrome and insulin resistance markers in patients with PHPT 1 year after parathyroidectomy. Copyright © 2011 AACE.


Meivar-Levy I.,Endocrine Institute
Methods in molecular biology (Clifton, N.J.) | Year: 2010

Regenerative medicine aims at producing new cells for repair or replacement of diseased and damaged tissues. Embryonic and adult stem cells have been suggested as attractive sources of cells for generating the new cells needed. The leading dogma was that adult cells in mammals, once committed to a specific lineage, become "terminally differentiated" and can no longer change their fate. However, in recent years increasing evidence has accumulated demonstrating the remarkable ability of some differentiated cells to be converted into a different cell type via a process termed developmental redirection or adult cells reprogramming. For example, abundant human cell types, such as dermal fibroblasts and adipocytes, could potentially be harvested and converted into other, medically important cell types, such as neurons, cardiomyocytes, or pancreatic beta cells. In this chapter, we describe a method of activating the pancreatic lineage and beta-cells function in adult human liver cells by ectopic expression of pancreatic transcription factors. This approach aims to generate custom-made autologous surrogate beta cells for treatment of diabetes, and possibly bypass both the shortage of cadaveric human donor tissues and the need for life-long immune-suppression.


Shi X.,Endocrine Institute | Han C.,Endocrine Institute | Li C.,Endocrine Institute | Mao J.,Endocrine Institute | And 12 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2015

Context: The WHO Technical Consultation recommends urinary iodine concentrations (UIC) from 250 to 499 μg/L as more-than-adequate iodine intake and UIC ≥500 μg/L as excessive iodine for pregnant and lactating women, but scientific evidence for this is weak. Objective: We investigated optimal and safe ranges of iodine intake during early pregnancy in an iodine-sufficient region of China. Method: Seven thousand one hundred ninety pregnant women at 4-8 weeks gestation were investigated and their UIC, serum thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroidperoxidase antibody (TPOAb), thyroglobulin antibody (TgAb), and thyroglobulin (Tg) were measured. Results: The prevalence of overt hypothyroidism was lowest in the group with UIC 150-249 μg/L, which corresponded to the lowest serum Tg concentration (10.18 μg/L). Prevalences of subclinical hypothyroidism (2.4%) and isolated hypothyroxinemia (1.7%) were lower in the group with UIC 150-249 μg/L. Multivariate logistic regression indicated that more-than-adequate iodine intake (UIC 250-499 μg/L) and excessive iodine intake (UIC ≥ 500 μg/L) were associated with a 1.72-fold and a 2.17-fold increased risk of subclinical hypothyroidism, respectively. Meanwhile, excessive iodine intake was associated with a 2.85-fold increased risk of isolated hypothyroxinemia. Moreover, the prevalence of TPOAb positivity and TgAb positivity presented a U-shaped curve, ranging from mild iodine deficiency to iodine excess. Conclusion: The upper limit of iodine intake during early pregnancy in an iodine-sufficient region should not exceed UIC 250μg/L, because this is associated with a significantly high risk of subclinical hypothyroidism, and a UIC of 500μg/L should not be exceeded, as it is associated with a significantly high risk of isolated hypothyroxinemia. Copyright © 2015 by the Endocrine Society.


PubMed | Endocrine Institute
Type: Journal Article | Journal: Rambam Maimonides medical journal | Year: 2016

Kallmann syndrome is named after Franz Joseph Kallmann, a German-born psychiatrist who described in 1944 twelve subjects from three families who presented with a syndrome of missed puberty, anosmia, and color blindness. Yet, several other eponyms for the same syndrome can be found in the literature. Despite the fact that Kallmann syndrome is the most recognized eponym, very little is known about the man for whom the syndrome is named. A biographical note on Franz Joseph Kallmann and his historical context is presented.


The Bethesda system for reporting thyroid cytopathology (TBSRTC) was developed in 2009 to standardize the terminology for interpreting fine-needle aspiration (FNA) specimens.A historical prospective case series design was employed. The study group included patients with a thyroid nodule classified as TBSRTC AUS/FLUS (B3) or FN/SFN (B4) in 2011-2012 in a tertiary university-affiliated medical center. Rates of surgery and malignancy detection were compared to our pre-TBSRTC (1999-2000) study.Of 3927 nodules aspirated, 575 (14.6%) were categorized as B3/B4. Complete data were available for 322. Thyroidectomy was performed in 123 (38.2%) cases: 66/250 (26.4%) B3 and 57/72 (79.2%) B4. Differentiated thyroid cancer was found in 66 (53.7%) patients: 30/66 (45.5%) B3 and 36/57 (63.2%) B4 (p=0.075). Operated patients were younger than the non-operated (B3: 52.416 vs. 59.713 years, p=0.009; B4: 51.715 vs. 60.514 years, p=0.042), and operated B3 nodules were larger than the non-operated (27.2 vs. 22.2 mm, p=0.014). Additional FNA was done in 160 patients (49.7%): 137/250 (54.8%) B3 and 23/72 (31.9%) B4 (p=0.002). The additional B3 nodules aspirations yielded a diagnosis of B2 in 84 patients (61.3%), B3 in 48 (35%), and B4 in 5 (3.6%). Of the 23 repeated B4 aspirations, B2 was reported in 5 (21.7%), B3 in 12 (52.2%), B4 in 4 (17.4%), and B6 in 2 (8.7%). The number of aspirated nodules was twice that reported in 1999-2000. The rate of indeterminate nodules increased from 6 to 14.6%, the surgery rate decreased from 52.3 to 38.2%, and the accuracy of malignancy diagnosis increased from 25.9 to 53.7%.The application of TBSRTC significantly improves diagnostic accuracy for indeterminate thyroid nodules, leading to higher rates of malignancy detection despite lower rates of thyroidectomies.


PubMed | Tel Aviv University, Rabin Medical Center and Endocrine Institute
Type: | Journal: Endocrinology, diabetes & metabolism case reports | Year: 2014

A 55-year-old male, with a positive medical history for hypothyroidism, treated with stable doses for years was admitted with subacute thyroiditis and a feeling of pain and pressure in the neck. Laboratory tests showed decrease in TSH levels, elevated erythrocyte sedimentation rate, and very high antithyroid antibodies. Owing to enlarging goiter and exacerbation in the patients complaints, he was operated with excision of a fibrotic and enlarged thyroid lobe. Elevated IgG4 plasma levels and high IgG4/IgG plasma cell ratio on immunohistochemistry led to the diagnosis of IgG4-mediated thyroiditis. We concluded that IgG4-thyroiditis and IgG4-related disease should be considered in all patients with an aggressive form of Hashimotos thyroiditis.IgG4-related disease is a systemic disease that includes several syndromes; IgG4-related thyroiditis is one among them.IgG4-thyroiditis should be considered in all patients with an aggressive form of Hashimotos thyroiditis.Patients with suspected IgG4-thyroiditis should have blood tested for IgG4/IgG ratio and appropriate immunohistochemical staining if possible.

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